The post-trauma appearance of immunosuppression is the major contributor to septic complications. Our longterm goal is to identify the altered cellular mechanisms which lead to post- trauma immunosuppression. Monocyte (M0) aberrations, particularly elevated production of prostaglandin E2 (PGE2), have been identified as pivotal in the mediation of post-trauma immunosuppression. Our laboratory showed that a disproportionate increase in the M0 subset expressing high densities of the high affinity receptor for IgG 1 & 3 (FcRI) is largely responsible for the post-trauma elevation of immunosuppressive PGE2. This FcRI+ M0 subset has distinct functional characteristics including major PGE2 secretion, major tumor necrosis factor (TNF) production and low antigen presenting capacity. Consequently, a post-trauma increase in this subset at the expense of the FcRI- facilitory M0 subset produces widespread M0 aberrations. Our hypothesis is that a shift in M0 functional subsets results in many of the post-trauma microenvironment which preferentially cause differentiation and/or activation of particular M0 subsets. We are proposing first, to examine other phenotypically identifiable M0 subsets (such as the complement C3b-4b receptor expressing M0 subset and the M0 subset constituently expressing high levels of HLA-DQ and DP) for similar post-injury proportional shifts which correspond to identifiable post-trauma M0 functional aberrations. Second, we are proposing to expand the M0 mediators monitored to include detection of IL-6, distinction and detection of Il-l alpha and IL-1 beta, and assessment of Transforming Growth Factor beta, as well as our current assessment of M0 PGE2, TNF, plasminogen activator and antigen presenting capacity. Third, we will examine induction of the identified Mo subsets by T cell subsets, lymphokines, or by biological stimuli to characterize any post-trauma alteration in the response capacity of the subsets and to determine if M0 dysfunction can be corrected by mediator activation. Finally, we will examine the effect of known trauma induced cytokines on the differentiation and activation of the promyelocytic cell line (HL- 60) to mature M0 and characterize any alteration in their phenotypic marker expression or function. These experiments may allow identification of immunosuppressed patients on the basis of detecting therapy could offset post-trauma immune dysfunction.